The outcome of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity.

backgroundWe investigate whether, in Swedish national registers, social and psychiatric outcomes for six major psychiatric and substance disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), anxiety disorder (AD), and schizophrenia (SZ) - reflect the primary genetic risk for each disorder and the level of genetic heterogeneity.

methodsWe utilize Genetic Risk Ratios - defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder - derived from Family Genetic Risk Scores. Poor social outcome was defined by a common factor of four variables: receipt of social welfare, sick leave, early retirement pension, and residence in a socially deprived area. Psychiatric outcome was defined as days of inpatient psychiatric hospitalization.

resultsWith poorer social outcomes, the primary genetic risks rose robustly for all disorders except SZ, as did the secondary genetic risks for DUD, AUD, and attention-deficit hyperactivity disorder. With poorer psychiatric outcomes, available only for BD and SZ, the primary genetic risks increased sharply. Overall, MD, AD, and BD became substantially more genetically heterogenous as their social outcomes became poorer, while for AUD, DUD, and SZ, the increase in heterogeneity was more modest. By contrast, with poorer psychiatric outcome, genetic risks for SZ became substantially more genetically homogeneous, with a similar but less robust trend seen for BD.

conclusionsDespite important differences between our primary disorders, social and psychiatric outcomes are often robust indices of genetic risk and can reflect the levels of genetic heterogeneity.